The long term goal of our research is to develop a point-of-care (POC) diagnostic test to help clinicians identify sites and/or subjects that are susceptible to periodontal disease progression. The primary objective of this project is to identify biomarkers of periodontal disease progression. The central hypothesis is that a combination of host analytes and subgingival species will be effective as biomarkers of periodontal disease progression. Periodontal diseases are the most common cause of tooth loss among adults in the United States and recent studies suggested that they increase the risk for systemic conditions such as cardiovascular diseases, diabetes, respiratory diseases and can affect reproductive outcome. Further, periodontal diseases progress through bursts of activity followed by periods of quiescence. Early accurate identification of individuals and/or sites that are undergoing active disease progression is critical to signal the need for immediate intervention to minimize tooth loss, allow for proper allocation of resources to treat susceptible individuals, and limit the potential systemic sequelae of these infections. However, there are no practical clinical means of identifying periodontal sites and/or subjects that are progressing. Better biomarkers of periodontal disease activity are urgently needed to improve periodontal disease diagnosis, guide therapy, monitor activity, and evaluate treatment response. Aim 1 will examine the longitudinal variability of levels of host biomarkers in GCF and saliva. Aim 2 will examine the diagnostic utility of GCF and salivary levels of host biomarkers and uncultivated and cultivable taxa in saliva and in subgingival biofilm samples for discriminating progressing and non-progressing periodontal sites and subjects. Aim 3 will determine the effects of periodontal therapy on the levels of salivary and GCF biomarkers and on uncultivated and cultivable taxa in saliva and in subgingival biofilms. Factors that strengthen this proposal include: 1) participation by two NIH Clinical and Translational Science Award centers (The Forsyth Institute and Michigan Center for Oral Health Research); 2) vast experience of both Centers in multiplex quantification of host biomarkers in oral fluids; 3) access to the newly developed RNA-oligonucleotide quantification technique (ROQT) for quantifying uncultivated and cultivable bacterial taxa; and 4) access to state-of-the-art bioinformatics cores to support analysis of large data sets. This project addresses the NIDCR's strategic interest in early detection and identification of risk factors for periodontal disease and reaffirms the center's commitment to facilitate the translation of science into clinical practice. Successful completion of this project will lead to validation of biomarkers that can be used in POC tests to help clinicians identify sites and subjects at risk for disease progression who require immediate intervention.